The present invention pertains generally to instruments used to inject medicaments or other materials into a body wall, tissue, chamber, or vessel. More particularly, a syringe system is provided that is capable of injecting, manually or automatically, precisely measured quantities of liquids into a body A plurality of needle designs are included for creating advantageously shaped or diffused clouds, streams, or jets of medicament, contrast agents or other liquids.
The direct introduction of a drug, compound, contrast agent, biologically active peptide, gene, gene vector, protein, or cells for therapy, into the tissues or cells of a patient can have significant therapeutic value. Injection has long been a popular, relatively non-invasive means for the direct introduction of various medicaments and other fluids and is becoming more popular as a means for non-invasive delivery of pharmaceutical preparations of peptides because it minimizes tissue trauma. Injection is also a practical delivery strategy for angiogenesis.
Angiogenesis is defined as the growth of new blood vessels. It is an important natural process occurring in the body, both in health and in disease. It occurs in the healthy body for healing wounds and for restoring blood flow to tissues after injury or insult. It can be affected by angiogenic growth factors such as VEGF (vascular endothelial growth factor) and Fibroblast Growth Factor (acidic or basic). Endothelial and vascular smooth muscle cells, and myocardial cells have low mitotic activity in normal adult coronary arteries and heart muscle. However, during growth and development, and under conditions of ischemia, hypoxia, inflammation or other stresses, these cells may begin to migrate and divide, especially in the microcirculation. This eventually results in the development of new intramuscular blood vessels. Naturally occurring endothelial growth factors with angiogenic potency, like FGF and VEGF, can induce angiogenesis by stimulating endothelial cell growth, differentiation and migration.
The delivery strategy of angiogenesis is a major issue limiting its widespread use. A number of strategies have been attempted but none have proven as practical as the transendomyocardial injection. Other approaches have certain disadvantages that make them less desirable. Intracoronary infusions, injection of angiogenic factors into the blood stream in the coronary arteries, while minimally invasive, cause systemic exposure to growth factors, which can have undesirable effects elsewhere in the body. In addition, intracoronary infusions cause little uptake of factors by the myocardium. Intrapericardial injections, injection of factors into the sac surrounding the heart, have potential to be used as a reservoir for continual delivery, but many receiving the treatment have also received CABG and no longer possess an intact pericardium. Also the procedure to make the injection is very difficult due to the anatomy of the pericardium. The transepicardial injection, injection directly into myocardium from the outside, requires open-chest surgery although there is potentially a thoracoscopic method, which is less invasive. The problems of the above approaches for delivery leave transendomyocardial injection as the approach that most reliably delivers the factors without waste of factors, open-chest surgery, or systemic exposure.
However, there are several problems with the current procedure of intramyocardial injection using a standard needle with a single end hole. First, a significant amount of material often exits the needle and leaves the myocardium retrogradely via the needle puncture tract. This phenomenon is hereafter referred to as “backflow”. This is a serious problem in that the angiogenesis-promoting factors are extremely expensive and if they are not introduced into the target area, they do not serve their desired function. Additionally, systemic exposure could produce problems such a hypotension, as the drug may interact with other areas of the body.
Another problem with the current procedure has to do with poor distribution of the factors. Convincing evidence has been observed that a traditional needle has a poor distribution of factors to the heart during injection. It is apparent, therefore, that there is a need for diffusionary needle having multiple holes which provides a greater and more controllable distribution of injectate in the area of injection.
Furthermore, the above identified problem pertaining to poor distribution of the factors may also be attributed to a vacuum effect created in the myocardial area when the needle is removed. This vacuum effect may draw injectate from the surrounding tissue back into the track formed by the needle. This effect may be lessened by providing a needle design whereby the outside surface of the needle prevents a seal from forming between the surface of the needle and the surrounding tissue. A diffusionary needle having multiple holes formed in the outer surface, a needle with a scored outer surface, or a combination of the two reduces this effect.
Not necessarily specific to angiogenesis, traditional injection methods and devices have failed to give the operating physician an acceptable degree of control over the size, shape and distribution of the injectate cloud. Conventional needle designs deliver the injectate to a single target site, thereby depositing an often higher than desired concentration of injectate, which must distribute itself naturally. In the case of certain peptides and pharmaceuticals, a high deposit concentration is potentially toxic if the concentration is sufficient to produce a biological response to the injected agent.
More specifically, traditional needles define an inner lumen leading from a reservoir, such as a syringe, to an opening in a distal, sharpened point. Once the tip of the needle has reached a target site, a physician or machine forces injectate through the opening. Control is achieved only by varying the rate at which the fluid is forced through the needle. In the case of a manually operated syringe, control is an imprecise matter of dexterity and muscle control. The resulting cloud of injectate at the injection site has a shape largely controlled by the density of the surrounding tissue and the flow rate of the stream leaving the needle. Moreover, as the partial pressure of injectate at the needle tip becomes high, there is a tendency for the injectate to follow the needle as it is withdrawn, thereby leaving the target site.
Accordingly, there continues to be a need in the art for new and better needles and injection systems, or devices suitable for injection of controlled amounts of therapeutic or diagnostic substances without substantial loss of injectate and without substantial damage to tissue, even during repeat injections.
There is a particular need for needles that are adapted for attachment to various types of catheters for such controlled delivery of therapeutic substances at remote locations within the body.
There is also a need for a method and a device which significantly yet controllably reduces the minimum quantity of injectate which a manual or automatic syringe may deliver.
Further, there is a need for an injection system that provides control over the stream or streams of injectate leaving the needle or a catheter. More specifically, there is a need for a needle or catheter which gives the operator the ability to manipulate the resulting cloud of injectate while the fluid is flowing from the needle, without having to move the needle longitudinally or transversely and risk causing injury to the target site.
Summarily, there is a need for an injection device that gives control over the concentration, pattern, and location of the deposition of an injectate.